Development of biodetection platform with magnetoresistive sensors andmagnetic nanopartcles

Abstract

Compared with traditional radioimmunoassay and fluoroimmunoassay for early diseases detection, the magnetic immunoassay utilizing magnetic nanoparticles as bio-labels and magnetic signal sensors as detectors has remarkable advantages because most biological samples exhibit no magnetic background and highly sensitive measurements can be performed. This thesis presents the development of biodetection platform taking advantage of the physical-and chemical-stability, low-toxicity, and environmentally-safety of magnetic iron oxide nanoparticles (IONPs) and the high-sensitivity, low-cost, and portable capabilities of magnetoresistive (MR) sensors. The first part explained why a magnetic biodetection platform is desirable, and what advantages it possesses. Then the magnetism of IONPs utilized in this detection system was introduced, followed by the introduction of main synthesis methods to obtain the desirable IONPs. The working principle of MR sensor was explained, and the recent advances about the biodetection platforms with various magnetoresistive sensors and magnetic IONPs labeling was reviewed. A brief summary of new contributions reported in this thesis was summarized. Then the establishment of home-made measurement setups for the characterization of MR sensor was described. The MR loops of MR sensors can be obtained with the instrument using two-point probe measurement, four-point probe measurement, or Wheatstone bridge measurement. The single MTJ sensor, MTJs array sensor, and the GMR spin valve sensor in Wheatstone bridge were characterized here. The magnetic IONPs were prepared through co-precipitation method and thermal decomposition method, and then surface-functionalized using citric acid and fatty acids to acquire carboxyl groups for the binding ability with biomolecules. The physical and chemical properties, sterilizing-treatment tolerability and biocompatibility of nanoparticles were studied. Furthermore, two new synthesis methods were developed to obtain novel magnetic gold/iron oxide nanocomposites for their potential use as magnetic bio-labels. A magnetic detection platform was built, and the detection of 10-nm superparamagnetic IONPs with MR sensor was first realized here. The output signal of the giant magnetoresistive (GMR) sensor in Wheatstone bridge exhibited log-linear function of the concentration of IONPs, making our sensing system suitable for use when ultra-small bio-labels are needed. The biodetection platform with MR sensor and IONPs was successfully developed and applied for the detection of antigen biomolecules. The feasibility of magnetic biodetection system, based on magnetic tunneling junction (MTJ) sensors and carboxyl-group functionalized IONPs, to detect AFP antigens (liver cancer biomarker) and p24 antigens (HIV biomarker) was demonstrated here for the first time. By taking advantages of its high sensitivity, low power consumption, low cost, and feasibility to be miniaturized, the development of magnetoresistive biodetection platform will bring revolutionary impact on the biodetection techniques for clinical early diseases diagnosis.