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Efforts on healthcare everywhere have led magnetoresistive biosensors to a fascinating field. One of its precious advantages is the creation of a cheap handheld point-of-care tool which in a few minutes can easily perform multiplexed diagnose the life-threatening diseases or monitoring chronically ill patients. In this biosensor, the magnetic nanoparticles are coated with chemical groups that will bind to the biomolecules, and then could be detected by magnetic sensor. The nanoparticle-biomolecule complexes react with 'probe' molecules that are immobilized onto the surface of the magnetoresistive sensors. Finally, the presence of the magnetic nanoparticles on the sensor surface produces a signal change of the magnetoresistive sensor by applying an external magnetic field [1]. Consequently, both the high magnetic moment nanoparticles such as α-Fe, CoFe, α-Fe@Fe3O4 nanoparticles, and high field-sensitivity magnetoresistive sensors are never-ending desired for enhancement of the biosensor resolution in detecting the bioanalytes. Among various magnetoresistive biosensors, planar Hall effect (PHE) sensor has received vast interest since it meets the needs for high sensing biosensor technology such as: high resolution owing to its small noise, small offset and linear response. To enhance the sensitivity of a PHE sensor, we have optimized both the sensor materials, and the sensor designs. In continuity development of the sensor sensitivity, we report here, the improved measurement configuration to enhance the sensitivity of a PHE sensor. The voltage change of the sensor causing by paramagnetic particles is calculated for a wide range of applied field. Thus, the critical field for maximum change of the voltage is deduced. In addition, the sensitivity of the sensor has been investigated as a function of the external magnetic field direction. By optimizing the measurement setup, the sensitivity of the sensor could be enhanced by one order in magnitude. The experimental setup for a hybrid alternative and continuous field is introduced for enhancing the sensitivity of the sensor. This optimizing method could be a paradigm easily adapted for enhancement of the sensitivity of other magnetoresitive biosensors. References [1] Adarsh Sandhu: New probes offer much faster results. Nature Nanotechnology, 2, (2007) 746.