Study Of Biosensor Based On Giant Magnetoresistance Effect

Giant magnetoresistance?GMR?effect has made great interest of many international scholars due to its huge application prospect,since it was reported by professor Albert Fert and Peter Grünberg in 1980s.GMR sensor based on giant magnetoresistance effect,has a wide range of potential applications in magnetic recording,magnetic-field sensors and stress sensors attributed to their advantages such as high sensitivity,quick response,small size and low cost,etc.Recently,a novel biosensor based GMR was developed via combining with immuno-magnetic beads technology.However,in present detection methods based on GMR biosensor,the sensor's surface was need to be modified by chemical for capturing the biomarker.The sensor did not avoid being contaminated and damaged by chemical reactive layer during the biomarker preparing,although there was some protective layer such as SiO_2.So,detection methods of GMR-based biosensors need to furtherly develop for protecting the GMR.In addition,with the development of microfluidic technology,GMR-based microfluidic biological detection system has also been greatly developed.However,almost these GMR-based microfluidic systems were only implemented for biomarker detection,the bio-sample need to be pretreated manually which will inevitably increase the detection error,sample consumption and detection time,and multi-functional bio-micro system based on GMR is still few.Based on this,this thesis firmly focuses on developing new detection method and integrated microfluidic system based GMR sensor for superparamagnetic beads and biomarker detection.This thesis consists of five aspects:theoretical model of superparamagnetic beads detection based on GMR,separable detection method based on GMR sensor for superparamagnetic beads and E.coli O157:H7 detecting,magnetic bead manipulation system based on micro magnetic device,integrated microfluidic system based on GMR and micro magnetic system.The major research result is as follow:1.The influence of the stray magnetic field generated by superparamagnetic beads on the MR of spin valve is studied based on the single domain GMR theoretical model and the theory of magnetism.Based on the simulation results,a GMR device with high performance applied to magnetic bead detection is designed and fabricated.2.A separable detection method based on GMR is designed,and firstly applied in quantitative detection of 1?m magnetic beads.When the protective film of GMR is 100 nm,magnetic bead with concentration is 0.1?g/mL can be detected,and 0.01?g/mL can be detected when the protective film is reduced to 20 nm.And then appling this detection method in detecting PSA and E.coli O157:H7,the results showed that the limit of detection of PSA could be up to 0.1 ng/mL,which meet the clinical requirement?4 ng/mL?,and the minimum detection limit of E.coli O157:H7 is up to 100 CFU/mL.At last,in separable detection method,the sensor can be avoided in the biological and chemical solution,so,the sensor can be kept good stability and long life.3.Micro spiral coil was employed for magnetic bead tapping.The micro trapping system was designed and used for trapping magnetic beads with diameter is 2.8?m and E.coli O157:H7 labeled with magnetic bead.The experimental results show that,when the excitation current is 500mA,the trapping ratio of magnetic beads can be up to 72%with flow rate is 5?L/min,and increased with the concentration of beads increasing.On the contrary,the trapping ratio of bacteria is reduced with the bacterial concentration increased,this resulted from the disperse of bacteria in the high concentration solution is not dispersed enough than in the low concentration,that weakened the immune efficiency of magnetic beads modifying with E.coli O157:H7.4.A magnetic bead sorting microfluidic system based on 3D micro coil and soft magnetic material is designed and fabricated.The magnetic field gradient is furtherly enhanced by adding the FeNi lines caculated by MagNet software.The experiment results show that when the excitation current is 200 mA and the flow rate of the magnetic beads is5?L/min,the sorting ratio of the magnetic beads can be up to 92.4%.The sorting ratio increases with the injected current increased,and relationship between the sorting ratio and concentration was independent with the concentration range of 0.1¹0?g/mL.The magnetic sorting system was also tested by sorting bead-labeled E.coli O157:H7.As the result shown,after linked with E.coli O157:H7,the effective volume of magnetic bead group was enlarged in flow,that increase the drag force,and the E.coli O157:H7 was without magnetism,the magnetic force was not increased to resist the drag force,so magnetic bead linked with E.coli O157:H7 are more difficult to sort than the pure magnetic beads.In addition,the maximum sort ratio can reach 78.4%with a concentration of 100 CFU/mL?the injected current is 200 mA,the flow rate is 0.5?L/min?,and the sorting ration is slightly reduced with the E.coli O157:H7 concentration increased.5.The integrated microfluidic system based on GMR sensor and micro magnetic sorting system is designed.The integration of micro magnetic separation system and magnetic bead detection system is integrated by employing PDMS technology.The experimental results show that the integrated GMR microfluidic system can successfully sort and detect E.coli O157:H7 with the detection limit is 300 CFU/mL.In addition,sorting and detecting E.coli O157:H7 can be implemented in 45 minutes by this integrated microfluidic system.It has the advantages of detecting rapidly,fewer test samples,less manual manipulation,so it is very likely to be used in clinical testing in future.