Research On Terahertz Biosensing Of Breast Cancer Markers

Early diagnosis and timely treatment of cancer is necessary for avoiding tragedy.In the case of the breast cancer,traditional diagnostic methods,such as mammary gland molybdenum target,ultrasonic diagnosis,and X-ray computed tomography,have made much achievement,but still have partly limited because of inevitable trauma damage,time-consuming,and low-cost performance.Thus,there is an urgent need to develop a label-free,high-sensitivity,non-destructive detection method to achieve early diagnosis of cancer.On the other hand,due to low photon energy of terahertz radiation and its high sensitivity to biomolecules,metamaterial(MM)-based THz sensors with novel structure and excellent characteristics exhibit some advantages of low-cost preparation,high-efficiency of micro analytes and label-free detection,and have been used for highly sensitive detection and recognition of trace cancer markers.In this thesis,two common markers in the serum of breast cancer patients,CA125 and CEA,are taken as the research objects.Combined with THz MM chips on a ultra-thin flexible substrate and biological modification technology,THz spectroscopic detection and micro/nano low-cost fabrication technology are used to effectively improve the sensitivity and specific selection of target molecules.The whole process,including simulation,fabrication,modification,measurement and application of sensor chips are carried out.The results show that the designed sensor exhibits some advantages of less consumption,high sensitivity and simple operation,thus expands the road for early diagnosis of breast cancer,and also opens a new way for the detection of trace biochemical substances.The main contents of this thesis are as follows:1.Using silicon and polyimide(PI)as the substrate,a metamaterial biosensor with a three-split ring resonator and a unit structure of 50 ?m was designed and simulated by using the finite element method in CST Microwave Studio.The results show that the silicon based MM structure has two resonances,which appear at 0.681 and 1.629 THz,respectively,while the polyimide-based metamaterial has only one resonance at 1.113 THz.In addition,the transmission changes due to variation of refractive index,thickness,and the duty ratio are also simulated.In the case of PI-based MM sensor,the simulated results show that the sensitivity S can reach 157 GHz/RIU and 198 GHz/RIU when the thickness of the coating layer is 2 ?m and 4 ?m,respectively.For silicon based metamaterials,the higher sensitivity is 88 GHz/RIU,which occurs at high frequency resonance.Finally,based on the simulation results,the fitting relationship between refractive index of coating layer and frequency shift of the resonance is given under the two different thicknesses of 2 and 4 ?m.2.In order to explore the reliability of the biosensor performance,two kinds of biosensors based on silicon and polyimide were prepared and measured with different concentrations of NaCl solutions.The results show that the properties of PI based metamaterials are obviously better than those of silicon based metamaterials,and can effectively distinguish the covering samples with refractive index gradient of 0.002.3.Two kinds of metamaterials were modified by 3-Mercaptopropionic acid,1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and Sulfo-N-Hydroxysuccinimide,etc.Firstly,the antibody is bonded on the surface of the metamaterial structure,and then the antigen is captured by the specific binding of antigen and antibody to achieve the specific modification,and then the specific detection of the biosensor is achieved.4.Blank,antibody modified and antibody antigen modified metamaterials were further measured by terahertz time-domain spectroscopy(THz-TDS).The results show that the designed THz MM sensor could effectively distinguish the antigen solution of 10,20,30,40 and 50 ng/?l.In addition,the resonance frequency presents a nonlinear red shift with increase of the sample concentration.The qualitative identification and quantitative.detection of the two cancer markers could be realized by combining the experimental data and the fitting formula.In summary,the terahertz metamaterial biosensor proposed in this thesis can effectively identify protein molecules such as cancer markers in serum of breast cancer.In addition,the flexible substrate has the advantages of low cost and simple operation,which provides a new idea for the development of THz metamaterial biosensors.