Highly-sensitive Cell Concentration Detection By Resonant Optical Tunneling Effect

Cell concentration can directly reflect the health state of human tissues and organs.Refractive index detection is becoming one of the research hotspots in biosensor research because of their advantages,e.g.label-free detection,real-time monitoring,high resolution and simple structure.Biosensors based on ROTE(Resonant Optical Tunneling Effect)can achieve high precision detection of cell concentration,accurately reflect the development and prognosis of pathological mechanism,and meet the needs of current biomedicine.The dissertation present the development of cell concentration detection technology based on typical optical detection methods(including LSPR,TFBG,optical fiber FP cavity),and their advantages and disadvantages are compared.The application and development based on ROTE are emphasized.First,the transmission matrix method(TMM)is used to deduce the mathematical formula of the sensing mechanism of light transmission in multilayer medium system.Through the mathematical analysis software Mathematica,the multilayer medium structure based on ROTE is simulated and analyzed.The RI sensitivity of the resonator is verified by changing the RI of the central slab,the RI sensitivity and Q value of the sensor are also characterized.The influence of material absorption on Q value of sensor is analyzed emphatically.Then,according to the simulation results of the ROTE five layer sensitive structure,the ROTE sensing unit is designed.And the material selection,the refractive index distribution,the size design and the preparation technology of the spin coating method are introduced in detail.The cell concentration detection scheme is designed based on the ROTE sensing unit.And the experimental platform of cell concentration is completed.Finally,here the top saturation method is adopted to narrow the spectral width of dip and to enhance the total Q factor.Performance calibration by using this method has shown the sensitivity of 19,000 nm/RIU and the total Q factor of 4,000.Experiments with hepatoma cells have obtained the sensitivity as high as 3.15 nm/(amol/ml)and the detection limit of 4×10~4 cells/ml.Compared with the reported optical cell sensors,this work is original due to the first use of the ROTE mechanism and is superior in the device performance.For instance,it enhances the sensitivity by about 40 times and the figure of merit(FOM)by about 20 times as compared to the state of the art.These make it highly potential for biomedical applications such as drug discovery,cell research and medical diagnoses.